RESUMEN
Combination antiviral therapy involving sofosbuvir (SOF) and simeprevir (SIM) is a treatment option in patients with genotype 1 chronic hepatitis C; however, the safety of this regimen in patients with decompensated cirrhosis is not established. Data from a combined treatment cohort of 2 large hepatology referral centers were evaluated to assess for safety and efficacy of SIM plus SOF with or without ribavirin (RBV) in patients with Child B or C cirrhosis. All (n = 42) patients included in the analysis had Child B (n = 35) or C (n = 7) cirrhosis and received 400 mg daily of SOF plus 150 mg daily of SIM, with (n = 7) or without (n = 35) RBV, for 12 weeks. Of the 42 patients in this cohort, 31 (74%) were male, 22 (52%) had failed prior treatments, and 28 (67%) were genotype 1a. Prior decompensating events included encephalopathy (57%), fluid overload (88%), or variceal hemorrhage (24%). Median Model for End-Stage Liver Disease score was 12 (range, 6-25). Treatment was well tolerated overall with more than one-half (57%) reporting no adverse events. In those reporting adverse events, the most common were fatigue (n = 6), insomnia (n = 4), headache (n = 5), nausea (n = 4), and grade 1 rash (n = 1). One patient developed chemical pancreatitis that did not require treatment discontinuation. Three of 7 patients who received RBV developed anemia, with 2 requiring blood transfusions and 1 requiring a dose reduction. No episodes of decompensation requiring hospitalization or deaths occurred on treatment. Of 42 patients, 38 (90%) patients had negative viral load at end of treatment (EOT), and 31 of 42 patients (74%) achieved sustained virological response 12 weeks after EOT; 10 of 10 patients (100%) with HCV genotype 1b achieved sustained virological response for 12 weeks (SVR12). In conclusion, SOF plus SIM was very well tolerated in patients with advanced Child B/C decompensated cirrhosis. Overall, 74% of patients achieved SVR12; 100% of patients with genotype 1b decompensated cirrhosis achieved SVR12.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Virus de Hepatitis/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Ribavirina/uso terapéutico , Simeprevir/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Anciano , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Genotipo , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Virus de Hepatitis/genética , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ribavirina/efectos adversos , Simeprevir/efectos adversos , Sofosbuvir/efectos adversos , Texas , Factores de Tiempo , Resultado del TratamientoRESUMEN
Variceal bleeding is a frequent and life-threatening complication of portal hypertension. The first episode of variceal bleeding is associated not only with a high mortality, but also with a high recurrence rate in those who survive. Therefore, management should focus on different therapeutic strategies aiming to prevent the first episode of variceal bleeding (primary prophylaxis), to control hemorrhage during the acute bleeding episode (emergency treatment), and to prevent rebleeding (secondary prophylaxis). These strategies involve pharmacological, endoscopic, surgical, and interventional radiological modalities. This article reviews management of acute variceal bleeding.
Asunto(s)
Endoscopía Gastrointestinal/métodos , Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/cirugía , Hipertensión Portal/complicaciones , Enfermedad Aguda , Urgencias Médicas , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/fisiopatología , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/fisiopatología , Humanos , Ligadura , Derivación Portosistémica Intrahepática Transyugular , Escleroterapia/métodosRESUMEN
Malnutrition in advanced cirrhosis may worsen liver function and increase susceptibility to infections. Immune-enhancing nutrition supplements (IENS) may be of value, but their safety in patients with decompensated cirrhosis and history of encephalopathy is unknown. We assessed the safety of Impact Recover (Novartis, St. Louis Park, MN), an orally palatable IENS, in 12 men with hepatic cirrhosis of Child-Turcotte-Pugh (CTP) class B or C, ages 40-60. On day 0, patients were evaluated serially for 6 hours after ingestion of 2 packets of Impact Recover. Despite a transient doubling of the blood ammonia, no cognitive abnormalities were noted on clinical assessment or psychometric testing. Subsequently, patients were instructed to ingest 3 packets per day of Impact Recover for 56 days, after which supplements were stopped. Patients were evaluated in a fasting state on days 0 (baseline), 56 (end of treatment), and 112 (follow-up). One patient was transplanted on day 21, and another died after an urgent cholecystectomy on day 30. The remaining 10 patients completed the study. Mean value of CTP score was 9 (range, 7-11) and mean value of model for end-stage liver disease (MELD) score was 14 (7-21), and there was no change after 8 weeks of IENS. Only 1 experienced transient worsening of encephalopathy after omitting lactulose. Performances on psychometric tests did not change. Transferrin levels increased rapidly with IENS, then returned toward baseline after IENS was stopped. Fasting insulin and peptide YY (PYY) levels also increased, but fasting glucose and hemoglobin A1C did not change. Trends in other nutrition and immune parameters did not reach significance. We conclude that acute and chronic administration of Impact Recover was well tolerated in cirrhotic patients with controlled encephalopathy. Further studies are justified to assess potential efficacy of long-term IENS in preventing infection and slowing progression in advanced cirrhosis.
Asunto(s)
Encefalopatías/complicaciones , Suplementos Dietéticos , Inmunidad , Cirrosis Hepática/terapia , Adulto , Amoníaco/sangre , Suplementos Dietéticos/efectos adversos , Ayuno , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Humanos , Insulina/sangre , Cirrosis Hepática/complicaciones , Cirrosis Hepática Alcohólica/terapia , Masculino , Persona de Mediana Edad , Péptido YY/sangre , Factores de Tiempo , Transferrina/análisisRESUMEN
OBJECTIVE: Liver transplantation has become an effective treatment for cirrhotic patients with early-stage hepatocellular carcinoma. We hypothesized that the quality of surveillance for hepatocellular carcinoma influences prognosis by affecting access to liver transplantation. METHODS: A total of 269 patients with cirrhosis and hepatocellular carcinoma were retrospectively categorized into 3 groups according to quality of surveillance: standard-of-care (n=172) (group 1); substandard surveillance (n=48) (group 2); and absence of surveillance in patients not recognized to be cirrhotic (n=59) (group 3). RESULTS: Three-year survival in the 60 patients who underwent liver transplantation was 81% versus 12% for patients who did not undergo transplantation (P<.001). The percentages of patients who underwent transplantation according to tumor stage at diagnosis (T1, T2, T3, and T4) were 58%, 35%, 10%, and 1%, respectively. Hepatocellular carcinoma was diagnosed at stages 1 and 2 in 70% of patients in group 1, 37% of patients in group 2, and only 18% of patients in group 3 (P <.001). Liver transplantation was performed in 32% of patients in group 1, 13% of patients in group 2, and 7% of patients in group 3 (P<.001). Three-year survival from cancer diagnosis in patients in group 3 (12%) was significantly worse than in patients in group 1 (39%) or group 2 (27%) (each P<.05). Eighty percent of patients in group 3 had subtle abnormalities of cirrhosis on routine laboratory tests. CONCLUSION: The quality of surveillance has a direct impact on hepatocellular carcinoma stage at diagnosis, access to liver transplantation, and survival.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Tamizaje Masivo/métodos , Femenino , Humanos , Cirrosis Hepática/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Pronóstico , Calidad de la Atención de Salud , Estudios RetrospectivosRESUMEN
Priority for "sickest first" liver transplantation (LT) in the United States is determined by the model for end-stage liver disease (MELD). MELD is a good predictor of short-term mortality in cirrhosis, but it can overestimate risk when international normalized ratio (INR) is artificially elevated by anticoagulation. An alternate prognostic index omitting INR is needed in this situation. We retrospectively analyzed survival data for 554 cirrhotic veterans referred for consideration of LT prior to December 1, 2003 (training group). Using logistic regression we derived a predictive formula for 90-day pretransplant mortality incorporating bilirubin and creatinine but omitting INR. We normalized this formula to the same scale as MELD using linear regression. This yielded MELD-XI (for MELD excluding INR) = 5.11 Ln(bilirubin) + 11.76 Ln(creatinine) + 9.44. Accuracy of MELD-XI was validated in a holdout group of 278 cirrhotic veterans referred after December 1, 2003, and in an independent validation dataset of 7,203 cirrhotic adults listed for LT in the United States between May 1, 2001, and October 31, 2001. MELD-XI and MELD correlated well in training, holdout, and independent validation cohorts (r = 0.930, 0.954, and 0.902, respectively). In the holdout cohort, c-statistics of MELD vs. MELD-XI for mortality were, respectively, 0.939 vs. 0.906 at 30 days;0.860 vs. 0.841 at 60 days; 0.842 vs. 0.829 at 90 days; and 0.795 vs. 0.797 at 180 days. In the independent validation dataset, c-statistics for MELD vs. MELD-XI as predictors of 90-day survival were, respectively, 0.857 vs. 0.843 in noncholestatic liver diseases and 0.905 vs. 0.894 in cholestatic liver diseases. Comparable MELD and MELD-XI scores were associated with comparable prognosis. In conclusion, MELD-XI, despite omission of INR, is nearly as accurate as MELD in predicting short-term survival in cirrhosis. In patients treated with oral anticoagulants, substitution of MELD-XI for MELD may permit more accurate assessment of risk and more rational assignment of "sickest first" priority for LT.
Asunto(s)
Anticoagulantes/uso terapéutico , Fibrosis/tratamiento farmacológico , Fibrosis/cirugía , Fibrosis/terapia , Hepatopatías/cirugía , Fallo Hepático/cirugía , Trasplante de Hígado/economía , Obtención de Tejidos y Órganos/métodos , Adulto , Anticoagulantes/farmacología , Femenino , Humanos , Hepatopatías/mortalidad , Fallo Hepático/mortalidad , Masculino , Persona de Mediana Edad , Asignación de Recursos , Riesgo , Listas de EsperaRESUMEN
BACKGROUND AND AIMS: The liver plays a central role in production and degradation of lipoproteins. Declining lipoprotein cholesterol may reflect deteriorating liver function. METHODS: We reviewed the records of 248 veterans with noncholestatic cirrhosis followed in our clinics or referred for liver transplantation between January 1, 1997 and October 31, 2002 (analysis period) and confirmed our findings prospectively in 165 noncholestatic cirrhotic veterans newly referred for liver transplantation between November 1, 2002 and May 1, 2004 (validation period). RESULTS: In the analysis group, albumin, bilirubin, INR, and Model for End-Stage Liver Disease (MELD) score correlated strongly with high-density lipoprotein (HDL) cholesterol, weakly but significantly with total cholesterol and very-low-density lipoprotein cholesterol (VLDL), and poorly with low-density lipoprotein cholesterol (LDL). Transplant-free mortality at 90, 180, and 365 days was 17/201 (8.5%), 19/173 (11.0%), and 38/119 (31.9%), respectively. Death at all 3 time points was associated with significantly lower initial levels of HDL, VLDL, and total cholesterol, but not LDL cholesterol. Of the lipoproteins, HDL was the best predictor of survival at 180 and 365 days (concordance statistics .86+/-.05 and .78+/-.05, respectively). By multivariate logistic regression, HDL cholesterol and MELD score were independent predictors of survival at 6 and 12 months. By Cox regression, HDL cholesterol below 30 mg/dL was associated with 3.4-fold increase in the hazard ratio for cirrhotic death. In the validation period, HDL cholesterol was confirmed to be significantly associated with death or transplantation at 6 or 12 months. CONCLUSIONS: HDL cholesterol in noncholestatic cirrhotic patients is a liver function test and an indicator of prognosis.
Asunto(s)
HDL-Colesterol/sangre , Cirrosis Hepática/diagnóstico , Biomarcadores , Colesterol/sangre , Femenino , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/cirugía , Pruebas de Función Hepática , Trasplante de Hígado , Masculino , Evaluación de Resultado en la Atención de Salud , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Despite the adoption of "sickest first" liver transplantation, pretransplant death remains common, and many early deaths occur despite initially low Model for End-stage Liver Disease (MELD) scores. From 1997-2003, we studied 507 cirrhotic United States veterans referred for consideration of liver transplantation to identify additional predictors of early mortality. Most of the patients were male (98%) with cirrhosis caused by hepatitis C and/or alcohol (88%). Data for 296 patients referred prior to February 27, 2002 (training group), were analyzed; findings were validated in 211 patients referred subsequently (validation group). In the training group, 61 patients (21%) died within 180 days without transplantation; their median initial MELD score was 21. MELD score, persistent ascites, and low serum sodium (<135 meq/L) were independent predictors of early mortality. In patients with a MELD score of less than 21, only low serum sodium and persistent ascites were independent predictors of mortality; for MELD scores above 21, only MELD was independently predictive. Prognostic significance of persistent ascites and low serum sodium for low MELD score patients was confirmed in the validation group. Risk varied continuously with worsening hyponatremia. Modifying MELD, by including points for persistent ascites and low serum sodium, improved prediction of early pretransplant mortality in low MELD score patients. In conclusion, persistent ascites and low serum sodium identify patients with cirrhosis with high mortality risk despite low MELD scores. Ascites, hyponatremia, and other findings indicative of hemodynamic decompensation merit further prospective study as prognostic indicators in patients awaiting liver transplantation, and should be considered in setting minimal listing criteria.